1. Field of the Invention
This invention relates to apparatus for precise metering of small amounts of fluids, particularly biological fluids, in an environment which dictates that there be no contamination from one sample to the next. Particularly the apparatus is designed for automatic dispensing of uniform amounts of blood sera from different patients onto a plurality of test surfaces, even though the liquid properties of the sera may vary widely from sample to sample in an unpredictable manner.
2. State of the Prior Art
In recent years, a number of automated systems for carrying out quantitative chemical analyses of fluid samples have been developed and these have proven particularly advantageous for use in clinical laboratories; especially in the analysis of blood. Systems based on continuous flow analysis in which sample, diluents and test reagents are mixed together and transported through the analyzer are very widely utilized. However, these continuous analyzers, such as, for example, the analyzer illustrated in U.S. Pat. No. 2,797,149, are complex and expensive, require skilled operators, necessitate considerable expenditure of time and effort in repetitive cleaning operations, and do not permit the use of very small quantities of sample, such as are used in microanalytical techniques. The dispensing of blood or other fluids into the reaction container has been a relatively simple operation only when the system uses liquid analysis exclusively.
Devices have been constructed to permit the metering of small amounts of fluids other than blood serum. U.S. Pat. No. 3,552,605 discloses a hand dispenser which has a vent or valve means for controlling the pressure within the container. However, both precision and automation is lacking, and the device does not contemplate the repetitious dispensing of a plurality of different samples. Apparatus which is automatic and precise is shown in U.S. Pat. No. 3,572,400, wherein a pen-like device deposits a high viscosity magnetic fluid on a substrate a drop at a time, in response to pressure delivered by a piston in contact with the magnetic fluid. However, such apparatus is not suitable and was not designed for the handling of blood sera, because the contact between the pressurizing means and the fluid either will contaminate the next sample, or require an inordinate amount of cleaning between samples.
The precise dropwise metering of other non-biological fluids onto a substrate is shown, for example, in U.S. Pat. Nos. 3,164,304; 3,341,087; and 3,810,779. However, because of the peculiar properties of blood sera and the need to dispense different samples from different sources one after another without contamination, such apparatus does not meet the requirements of this invention.
Patents relating to the pressure metering of liquids by the alteration of the volume of a container such as a bellows include U.S. Pat. Nos. 194,010; 2,665,825; 3,323,689; and 3,618,829. These, however, are not designed to provide the precision required for biological fluids. Patents showing such metering by means of a piston mechanism such as a syringe include U.S. Pat. Nos. 2,946,486; 3,367,746; and 3,615,240.
Cup-like devices have been constructed for the dispensing of a variety of liquids including blood sera. Representative examples include those described in U.S. Pat. Nos. 1,326,452; 2,204,471; 2,586,513; 2,802,605; 3,449,081; 3,106,845; 3,460,529; 3,540,857 and 3,832,135 (FIGS. 22 and 23). In the case of blood sera, these devices do not provide repetitive dispensing of microsized drops substantially uniform in volume, regardless of variations in surface tension and viscosity that may be characteristic of blood sera taken from different patients. That is, these devices do not contemplate both (1) the formation of precise droplets as small as 1-30 .mu. l and/or (2) the use of the same container design for the dispensing of a variety of samples demonstrating varying properties.
Metering of serum by pressurizing the air above a container to force 10.sup.-.sup.4 liters of serum out through a siphon is shown, for example, in U.S. Pat. No. 3,650,437. However, the siphon is not properly constructed to permit the formation of pendant drops. Instead, the serum is ejected from the siphon onto a laboratory slide.
Other devices have been developed for dispensing blood sera, but little attention has been directed to the provision for repeated accuracy in such dispensing. Instead, sample size is controlled by treating the substrate upon which the blood serum is dispensed. Examples of such devices include those disclosed in U.S. Pat. No. 3,036,893.
Patents pertinent only to the background of dispensing containers in general include U.S. Pat. Nos. 2,058,516; 2,363,474; 2,598,869; 2,599,446; 2,721,008; 3,141,574; 3,190,731; 3,300,099; and 3,645,423.